The ability to induce changes in cell membrane properties is nowadays considered an additional mechanism to explain the pharmacological effects of non-steroidal anti-inflammatory drugs (NSAIDs). We previously demonstrated that the NSAID Licofelone, a dual cyclooxygenase/5-lipoxygenase inhibitor, triggers apoptosis in HCA-7 colon cancer cells independently from the inhibition of these enzymes. Here, we provide evidence that, in HCA-7 cells, the pro-apoptotic effect of this drug relies, at least in part, on its ability to inhibit epidermal growth factor receptor (EGFR) signalling by a decrease of cell membrane fluidity. Indeed, Licofelone induced a relevant change in the relative proportions of some saturated, monounsaturated and polyunsaturated fatty acids constituting HCA-7 phospholipid fraction, and significantly increased the levels of cholesterol in HCA-7 cell membrane. All of these changes resulted in a remarkable decrease of membrane fluidity. Such phenomenon was associated with the block of EGFR kinase activity and of its downstream targets, the p44-42 mitogen-activated protein kinase (MAPK) and AKT cascades, whose inhibitions were found to induce apoptosis in HCA-7 cells. Overall, these findings provide a new additional mechanism by which NSAIDs are effective toward colon cancer cells.

Tavolari S, Munarini A, Storci G, Laufer S, Chieco P, Guarnieri T. (2012). The decrease of cell membrane fluidity by the non-steroidal anti-inflammatory drug Licofelone inhibits epidermal growth factor receptor signalling and triggers apoptosis in HCA-7 colon cancer cells. CANCER LETTERS, 321(2), 187-194 [10.1016/j.canlet.2012.02.00].

The decrease of cell membrane fluidity by the non-steroidal anti-inflammatory drug Licofelone inhibits epidermal growth factor receptor signalling and triggers apoptosis in HCA-7 colon cancer cells.

TAVOLARI, SIMONA;MUNARINI, ALESSANDRA;STORCI, GIANLUCA;CHIECO, PASQUALE;GUARNIERI, TIZIANA
2012

Abstract

The ability to induce changes in cell membrane properties is nowadays considered an additional mechanism to explain the pharmacological effects of non-steroidal anti-inflammatory drugs (NSAIDs). We previously demonstrated that the NSAID Licofelone, a dual cyclooxygenase/5-lipoxygenase inhibitor, triggers apoptosis in HCA-7 colon cancer cells independently from the inhibition of these enzymes. Here, we provide evidence that, in HCA-7 cells, the pro-apoptotic effect of this drug relies, at least in part, on its ability to inhibit epidermal growth factor receptor (EGFR) signalling by a decrease of cell membrane fluidity. Indeed, Licofelone induced a relevant change in the relative proportions of some saturated, monounsaturated and polyunsaturated fatty acids constituting HCA-7 phospholipid fraction, and significantly increased the levels of cholesterol in HCA-7 cell membrane. All of these changes resulted in a remarkable decrease of membrane fluidity. Such phenomenon was associated with the block of EGFR kinase activity and of its downstream targets, the p44-42 mitogen-activated protein kinase (MAPK) and AKT cascades, whose inhibitions were found to induce apoptosis in HCA-7 cells. Overall, these findings provide a new additional mechanism by which NSAIDs are effective toward colon cancer cells.
2012
Tavolari S, Munarini A, Storci G, Laufer S, Chieco P, Guarnieri T. (2012). The decrease of cell membrane fluidity by the non-steroidal anti-inflammatory drug Licofelone inhibits epidermal growth factor receptor signalling and triggers apoptosis in HCA-7 colon cancer cells. CANCER LETTERS, 321(2), 187-194 [10.1016/j.canlet.2012.02.00].
Tavolari S; Munarini A; Storci G; Laufer S; Chieco P; Guarnieri T.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/113266
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